Investigating the Significance of Nocturnal Blood Pressure Patterns in Children with Chronic Kidney Disease

PROJECT SUMMARY
This is an initial submission of a K23 application by Dr. Christine Bakhoum, under the mentorship of Dr.
Joachim Ix at the UC San Diego. Through this proposal, Dr. Bakhoum intends to establish herself as an
independent investigator studying blood pressure (BP) patterns in pediatric chronic kidney disease (CKD).
Candidate: Dr. Bakhoum’s training objectives include; 1) become proficient in the research applications of
pediatric ambulatory blood pressure monitoring (ABPM) data, 2) develop skills in advanced biostatistical
methods, 3) acquire expertise in pediatric clinical trial design and implementation, and 4) advance her
professional development. Dr. Bakhoum will accomplish these objectives through mentorship, coursework, and
participation in workshops and steering committees. She has assembled a multidisciplinary team of scientists
including her primary mentor Dr. Joachim Ix, an expert in clinical trials in CKD, Dr. Dena Rifkin, a leader in
hypertension and the application of ABPM, Dr. Adriana Tremoulet, a pediatric clinical trialist, and Dr. Ronit
Katz, a PhD level biostatistician who works closely with her mentoring team.
Research: A diagnosis of CKD in childhood portends high risk for cardiovascular disease (CVD) and mortality
in early adult life. Thus, identifying modifiable risk factors for progression to end-stage kidney disease (ESKD)
is critical. In adults, ABPM data demonstrates that loss of the physiologic decrease in BP at night compared to
daytime, or BP non-dipping, is associated with kidney function decline and CVD. While non-dipping is
prevalent in children with CKD, the definition of dipping in pediatrics is arbitrary and adopted from the adult
literature. Dr. Bakhoum’s preliminary work demonstrated that blunted nocturnal dipping may have adverse
consequences (i.e. proteinuria), that the thresholds for these consequences may be different for systolic vs.
diastolic BP, and that kidney sodium mishandling may play a role in the pathophysiology. She hypothesizes
that nocturnal BP change is, in part, caused by impaired daytime sodium excretion, and is a modifiable risk
factor for progression to ESKD in children with CKD. In Aim 1, Dr. Bakhoum will evaluate the association of
nocturnal BP patterns with risk of ESKD in the Chronic Kidney Disease in Children (CKiD) study. In Aim 2, she
will recruit a cohort of 85 children with CKD and evaluate the association of the ratio of daytime to nighttime
sodium excretion with dipping patterns. Of this cohort, she will recruit 26 children with hypertension and non-
dipping who will continue to Aim 3. In Aim 3, she will conduct a randomized crossover study to test whether
nighttime administration of BP medications can restore nocturnal BP dipping in children with CKD. The results
of this proposal will provide a new framework for the interpretation of nocturnal BP in children with CKD and
will serve as a foundation for future clinical trials to investigate whether nighttime dosing of anti-hypertensive
medications can improve clinical outcomes in this population.

Grant Number: 5K23DK129836-06
NIH Institute/Center: NIH
Principal Investigator: Christine Bakhoum